Field of the Disclosure
The technology relates to polymer parts as used for microfluidic devices, targets for Matrix Assisted Laser Desorption Ionisation (MALDI) mass spectrometry, and other applications where good control of the wetting properties of at least one surface of a polymer part is needed.
Additives have been used to modify the bulk and surface properties of polymers since the beginning of polymer sciences. For example, softeners are applied to polyvinyl chlorides (PVC) to modify the properties of the brittle base material in applications where flex and elongation before break are needed. In addition, polymers have been modified with additives to protect them against oxidative stress or ultraviolet radiation. Furthermore, some hydrophobic additives have been used to improve the melt-flow properties in order to allow easier processing, preventing a polymer from shear stressed during processing.
In each case, the amount of additives needed was optimized to achieve each of the desired properties and combinations thereof. However, the large amount of additive required (for example, in the PVC compositions referred to above, 30% of the total weight of the composition is additives) can lead to an undesirable result in that such additives accumulate after a certain time of storage at the surface on the injection moulded or extruded article, potentially making such compounds or compositions unstable.
Description of the Related Art
One particular application of polymers having additives applied thereto is for MALDI mass spectrometry. MALDI is based on incorporating an analyte into a special matrix, usually an organic acid crystal, which permits laser desorption of the analyte in the instrument. The matrix assists the process in two primary ways. Firstly, the open crystal structure of the matrix readily absorbs the analyte and serves to allow the analyte to be spotted onto the surface of a MALDI target where it dries into a solid spot. Secondly, during the laser desorption stage of the analytical process the organic acid matrix ionises the analyte by proton transfer when both are in a vapour phase so that the molecular weight fractions of the analyte can be detected, for example in a time-of-flight mass spectrometer. The matrix can be pre-spotted as a liquid onto the MALDI target, with subsequent deposition of the analyte also as a liquid; or the matrix and analyte may be mixed together and spotted at the same time. The spotted liquid droplets are then allowed to dry and solidify. Once dried, the MALDI target can be arranged in the mass spectrometer and the analyte is released by scanning a laser over each spot in turn to desorb the analyte from the matrix. The laser assumes the spots are centred on precise grid locations on the target and that the spots have a defined diameter. Deviations from this result in poorer performance of the instrument, since, for example, a lesser quantity of analyte may be desorbed. An important part of the design of the top surface of a MALDI target plate is therefore how to ensure that the spots centre correctly on the grid locations during spotting, and remain in position during the subsequent drying process.
MALDI and specifically how to design the MALDI target plates is discussed extensively in the literature. A MALDI target generally takes the form of a rectangular format substrate with a square grid array of spot locations, e.g. 48 in a 6×8 array, 96 in a 12×8 array. The substrates were conventionally made of metal, for example stainless steel. These solid metal targets are re-useable, since they can be cleaned chemically and physically after use. Surface treatments are used to make the spotting surface generally hydrophobic to ensure that when the spots are deposited the liquid has a large contact angle and the spot remains localised where it is deposited during its drying phase. MALDI targets have been developed so that localised hydrophilic areas are arranged at the intended spot locations, so that when the liquid spots are deposited on the spotting surface they are effectively anchored at these hydrophilic points, thereby ensuring that the spot array of dried spots are precisely located at the intended laser sampling points. Local oxidization of the metal spotting surface can for example cause local hydrophilic regions to form in a more hydrophobic general area provided by the metal. Another approach is to define the spotting locations physically, e.g. with shallow wells, in the spotting surface.
In recent years MALDI targets based on polymer substrates have been developed. These are generally single use parts. Polymer substrates can have natively hydrophobic surfaces, or have their surfaces treated by plasma treatment to achieve a desired degree of hydrophobicity. In other designs, the polymer substrates have their spotting surface coated with a suitable material to provide the desired hydrophobicity or combination of hydrophobicity and hydrophilic anchor points. The coating may be a metal coating for example. It is also known to provide a substrate in which the bare surface is hydrophilic and then to selectively coat the bare surface with a hydrophobic material leaving small areas of the bare surface to form the anchor points. For example, it is known to use PTFE coating or coating with organic-inorganic sol gel nanocomposite materials using the coating method described in the literature. Coating of the grid locations is avoided by using a suitable lithographic process, e.g. covering the grid locations with a lacquer or photoresist prior to coating the remainder of the surface, which is then removed after coating to reveal the bare surface at the grid locations.
Moreover, plasma treatment of polymer surfaces is also an established technique for imposing controlled modification of the degree of hydrophobicity of polymer surfaces, and this can be used on its own, or more likely in combination with other techniques during manufacturing to achieve the desired surface hydrophobic/hydrophilic specification for a MALDI target made from a polymer substrate.
The use of hydrophobic small molecules, such as fatty acid or lipid type surface treatments to generate hydrophobicity on the surface of a polymer, is generally known in the art. However, in the techniques of the prior art, these small molecules have been applied to a target surface using a dip coating process from a solvent (methanol) solution. The application of the lipid by such wet coating methods can result in uneven deposition of the lipid. In addition, although a hydrophobic surface can be made using this technique the final contact angle variation within one target may easily vary, therefore rendering any subsequent automated analyte deposition unreliable. The advantages and inherent tight tolerances of an automated process are described in the literature.
Other known techniques for creating hydrophobic surfaces include deposition of PTFE layers or printing hydrophobic organic polymer layers. Although these techniques may impart hydrophobicity in the target's surface, the full extent of their implications with respect to the complete MALDI process has not been considered. For example, organic inks or coatings always contain additives (wetting agents, surfactants, defoamers, stabilisers etc) and residual monomers and such molecules can be regarded as potential contaminants in mass spectrometry. The limitations of PTFE coating and its layer thickness are discussed specifically in the literature.
The migration of polymeric materials and clays from the bulk to the surface of a polymer is known in the art. However, as can be understood from the above, it is generally thought that there is a great degree of control over the surface properties, and many ways to make a surface with the desired hydrophobic and hydrophilic properties. However, although this is true at the point of manufacture, the inventors have conducted long term stability tests on polymer substrates of the type used for MALDI targets and found that the degree of hydrophobicity of the surface slowly changes over time, as measured for example, one month, 3 months, 6 months and 12 months after manufacture. Many of these products should therefore be disposed of if not used soon enough after manufacture, or end up being used when their surface properties no longer meet specification.